Leiomioma cutáneo atípico en un paciente con leiomiomatosis cutánea y mutación de la enzima fumarato hidratasa / Atypical leiomyoma in a patient with cutaneous leiomyomatosis and mutation of the enzyme fumarate hydratase

Se presenta un varón de 56 años con un leiomioma atípico en el contexto de una leiomiomatosis cutánea, con antecedentes familiares de miomatosis uterina y con estudio genético que revela una mutación en el gen de la enzima fumarato hidratasa, sin que hasta el momento presente ningún tipo de neoplasia maligna renal. El leiomioma atípico es un tumor poco frecuente, que usualmente ocurre de forma aislada, siendo excepcional la presentación en pacientes con leiomiomatosis cutánea. Es ampliamente conocida la relación de la mutación de la enzima fumarato hidratasa con leiomiomas mútiples, miomas uterinos y el mayor riesgo de desarrollar cáncer renal; sin embargo, el papel de esta mutación en el desarrollo de leiomiomas atípicos es por hoy imposible de esclarecer debido a los escasos casos recogidos en la literatura.

We report the case of a 56 year-old male with an atypical leiomyoma in the context of a cutaneous leiomyomatosis and a family history of uterine leiomyomatosis. The genetic study revealed a mutation in the gene for the enzyme fumarate hydratase, but he has not had any renal malignancy so far. Atypical leiomyoma is a rare tumor that usually presents as a single lesion and is exceptional in patients with cutaneous leiomyomatosis. The relation between fumarate hydratase enzyme mutations with multiple leiomyomas, uterine leiomyomatosis and an increased risk of developing kidney cancer is widely known. However, the role of these mutations in the development of atypical leiomyomas is still impossible to clarify given the few cases reported in the literature.

Superoxide dismutase and lipid hydroperoxides in blood and endometrial tissue of patients with benign, hyperplastic and malignant endometrium

Epidemiological and experimental data point to involvement of oxygen derived radicals in the pathogenesis of gynecological disorders, as well as in cancer development. The objective of the present study was to examine changes in activities and levels of copper/zinc superoxide dismutase (CuZnSOD) and lipid hydroperoxides (LOOH) in blood and endometrial tissue of patients diagnosed with uterine myoma, endometrial polypus, hyperplasia simplex, hyperplasia complex and adenocarcinoma endometrii. The results of our study have shown decreased SOD activities and unchanged SOD protein level in blood of all examined patients in comparison to healthy subjects. Decrease of both SOD activity and level was found in endometrium of patients with hyperplasia simplex, hyperplasia complex and adenocarcinoma in comparison to women with polypus or myoma. LOOH level was elevated in both tissues of patients with hyperplasiaor adenocarcinoma in comparison to healthy subjects or patients with benign diagnosis. Our findings suggest that the decrease in SOD activity and level, as well as the increase in LOOH level, in patients with gynecological disorders, render these patients more susceptible to oxidative damage caused by reactive oxygen species (ROS). An imbalance in ROS formation and SOD level may be important in the pathogenesis and/or perpetuation of tissue damage in gynecological patients. Since evidence suggests that SOD may be a therapy target for cancer treatment, our findings provide a basis for further research and options for clinical applications.

Resultados epidemiológicos e experimentais apontam para o envolvimento dos radicais derivados do oxigênio na patogênese das moléstias ginecológicas, assim como no desenvolvimento do câncer. O objetivo do presente estudo foi o de examinar as alterações nas atividades e níveis de Cu/Zn superóxido dismutase (CuZnSOD) e hidroperóxidos lipídicos (LOOH)no sangue e tecido endometrial de pacientes diagnosticados com mioma uterino, pólipo endometrial, hiperplasia simplex, hiperplasia complex e adenocarcinoma do endométrio. Os resultados de nosso estudo mostraram atividades de SOD diminuídas e nível de SOD proteína inalterado no sangue de todos os pacientes examinados em comparação a indivíduos saudáveis. Diminuição de ambos, atividade de SOD e nível protéico, foram encontrados no endométrio de pacientes com hiperplasia simplex, hiperplasia complex e adenocarcinoma em comparação às mulheres com pólipos e/ou mioma. O nível de LOOH estava elevado em ambos os tecidos de pacientes com hyperplasia e adenocarcinoma em comparação a indivíduos saudáveis ou pacientes com diagnóstico benigno. Nossos resultados sugerem que um decréscimo na atividade e nível protéico de SOD, assim como um incremento no nível de LOOH, em pacientes com desordens ginecológicas, tornam esses pacientes mais susceptíveis ao dano oxidativo causado pelas espécies reativas de oxigênio (ROS). Um desequilíbrio na formação de ROS e no nível de SOD pode ser importante na patogênese e/ou perpetuação do dano tecidual em pacientes ginecológicos. Desde que existe evidência de que SOD pode ser um alvo para terapia de câncer, nossos resultados fornecem uma base para futura pesquisa e opções para aplicações clínicas.

Lipid peroxidation and antioxidant status in blood of patients with uterine myoma, endometrial polypus, hyperplastic and malignant endometrium

Oxidative stress is considered to be involved in pathogenesis of many disorders of the female genital tract. In this study, we explored the lipid peroxidation levels and antioxidant enzyme activities in women diagnosed with different forms of uterine diseases in order to evaluate the extent of oxidative stress in blood of such patients. Blood samples of healthy subjects and gynecological patients were collected and subjected to assays for superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and lipid hydroperoxides. The results show that alterations of measured parameters vary with the enzyme type and diagnosis. However, both reduction in antioxidants and elevation of lipid peroxidation were observed in general. Lipid hydroperoxides level was negatively correlated to superoxide dismutase and glutathione peroxidase activities, as well as positively correlated to catalase activity. In addition, the lipid hydroperoxides/ glutathione peroxidase ratio was found to be increased, according to the type of uterine disease. The obtained results show that perturbation of antioxidant status is more pronounced in blood of patients with premalignant (hyperplastic) and malignant (adenocarcinoma) lesions, compared to those with benign uterine changes such as polypus and myoma.

Niveles de superóxido dismutasa y catalasa en enfermedades del anciano / Dismutase and catalase superoxide levels in pathologies of the elderly

Se han determinado los niveles de superóxido dismutasa (SOD) y catalasa (CAT) en 420 individuos de uno y otro sexo y edades comprendidas entre 50 y 93 años. De ellos, 126 que no mostraban ninguna enfermedad relevante se utilizaron como grupo control. Los 294 restantes mostraban diferentes trastornos: alteraciones del sistema vascular (insuficiencias coronarias, hipertensión, infarto, etc.), alteraciones del sistema osteoarticular (artritis, polialtralgias, osteoporosis, etc.), miomas, afecciones, prostáticas, enfermedad pulmonar obstructiva crónica (EPOC) y accidente cerebral vascular agudo (ACVA). Para valorar SOD se utilizó el método de minami y Yoshikawa y el método de Aebi para valorar CAT. Métodos estadísticos: ANOVA y "t" de Student. En la población control se han obtenido: 1) niveles de SOD y CAT más elevados en mujeres que en varones. 2) la actividad de CAT disminuye con la edad. En la población con patologías: 3) la actividad de SOD está elevada en cardiovascular, miomas, EPOC y ACVA. 4) la actividad de CAT desciende en cardiovascular, próstata, EPOC y ACVA. 5) en osteoarticular actividad normal de SOD y CAT, aunque SOD desciende con la edad, CAT desciende con la edad en cardiovascular y EPOC. En general el comportamiento de ambos enzimas tiende a conseguir un equilibrio en el sistema antioxidante